We have uncovered derangements of the rat retinal pigment epithelium in early streptozotocin-induced diabetes which may be related to the breakdown of the blood-retina barrier which precedes the development of frank diabetic retinopathy in man. Between 3 and 5 weeks after onset of hyperglycemia, there is an abnormal entry of fluorescein into the cytoplasm of pigment epithelial cells together with a statistically significant increase in plasma membrane surface area at the basal aspect of the pigment epithelial cells. We propose to follow up these initial findings by undertaking a comprehensive series of investigations. We will apply the methods of electron microscopic morphometry, quantitative fluorescence microscopy, and quantitative histochemistry to define the onset and evolution of these structural and functional abnormalities in the pigment epithelium of spontaneously and streptozotocin-diabetic rats, to search for related changes in retinal blood vessels, and to characterize the effect of diabetes on essential metabolic functions of the pigment epithelium and neural retina. The results of the study will permit evaluation of the significance of the previously observed changes in the diabetic retina. Of equal importance, needed information will be acquired relating structural and functional properties of cells comprising the blood-retina barrier.